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{{Short description|Pharmaceutical drug}}
{{Drugbox
{{Use dmy dates|date=February 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 461094948
| verifiedrevid = 461094948
| IUPAC_name = 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy- 26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy- 7,9-ethano-12,15-methano-9''H'',15''H''-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4''H'')-one
| image = Eribulin.svg
| image = Eribulin.svg
| width = 300
| width = 300
| alt =
| caption =
| USAN = eribulin mesylate
| JAN = eribulin mesilate


<!--Clinical data-->
<!-- Clinical data -->
| tradename = Halaven
| pronounce =
| tradename = Halaven, Mevlyq
| Drugs.com = {{drugs.com|CDI|eribulin}}
| Drugs.com = {{drugs.com|monograph|eribulin-mesylate}}
| MedlinePlus = a611007
| MedlinePlus = a611007
| licence_EU = yes
| DailyMedID = Eribulin
| pregnancy_AU = D
| licence_US = Eribulin
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Eribulin (Halaven) Use During Pregnancy | website=Drugs.com | date=22 October 2019 | url=https://www.drugs.com/pregnancy/eribulin.html | access-date=9 July 2020}}</ref>
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = D
| pregnancy_category =
| routes_of_administration = [[Intravenous]]
| pregnancy_category =
| class = [[Antineoplastic agent]]
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| ATC_prefix = L01
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_suffix = XX41
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref name="CA Halaven PI" />
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Halaven 0.44 mg/ml solution for injection | website=(emc) | date=16 January 2023 | url=https://www.medicines.org.uk/emc/product/4517/smpc | access-date=16 December 2023}}</ref>
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Halaven FDA label" />
| legal_status =
| legal_EU = Rx-only
| routes_of_administration = Intravenous
| legal_EU_comment = <ref name="Halaven EPAR">{{cite web | title=Halaven EPAR | website=[[European Medicines Agency]] (EMA) | date=17 March 2011 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/halaven | access-date=16 December 2023}}</ref><ref name="Mevlyq EPAR">{{cite web | title=Mevlyq EPAR | website=[[European Medicines Agency]] (EMA) | date=9 February 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mevlyq | access-date=19 February 2024}}</ref><ref>{{cite web | title=Mevlyq product information | website=Union Register of medicinal products | date=13 February 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1789.htm | access-date=19 February 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only<ref>{{cite press release | title=Eisai Announces Japan Launch Of Anticancer Agent Halaven | publisher=Eisai Co., Ltd. | date=19 July 2011 | url=https://www.eisai.com/news/news201155.html | access-date=15 February 2021}}</ref><ref>{{cite press release | title=Anticancer Agent Halaven Approved For Treatment Of Locally Advanced Or Metastatic Breast Cancer In China | publisher=Eisai Co., Ltd. | date=17 July 2019 | url=https://www.eisai.com/news/2019/news201952.html | access-date=15 February 2021}}</ref>


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism =
| metabolism =
| metabolites =
| elimination_half-life =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =
| excretion =


<!--Identifiers-->
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 253128-41-5
| CAS_number = 253128-41-5
| ATC_prefix = L01
| CAS_supplemental =
| ATC_suffix = XX41
| PubChem = 11354606
| ATC_supplemental =
| IUPHAR_ligand =
| PubChem = 17755248
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| DrugBank = DB08871
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21396142
| ChemSpiderID = 24721813
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = LR24G6354G
| UNII = LR24G6354G
| KEGG_Ref =
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1237028
| KEGG = D08914
| ChEBI_Ref =
| ChEBI = 63587
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1683590
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = E7389, ER-086526, NSC-707389


<!--Chemical data-->
<!-- Chemical and physical data -->
| IUPAC_name = 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy- 26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy- 7,9-ethano-12,15-methano-9''H'',15''H''-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4''H'')-one
| chemical_formula =
| C=40 | H=59 | N=1 | O=11
| C=40 | H=59 | N=1 | O=11
| SMILES = CC1CC2CCC3C(=C)CC(O3)CCC45CC6C(O4)C7C(O6)C(O5)C8C(O7)CCC(O8)CC(=O)CC9C(CC(C1=C)O2)OC(C9OC)CC(CN)O
| molecular_weight = 729.90 g/mol
| smiles = O=C1C[C@@H]2[C@H]([C@H](O[C@H]2C[C@H]3O[C@H](C[C@H](C3=C)C)CC[C@H]4C(C[C@@H](O4)CC[C@]5(O6)C[C@@H]([C@@H]7O5)O[C@H]([C@H]7O[C@]8(CC9)[H])[C@@H]6[C@@]8([H])O[C@H]9C1)=C)C[C@@H](CN)O)OC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C41H61NO11/c1-20-12-26-7-9-29-21(2)13-25(46-29)6-5-11-41-18-34-37(52-41)38-39(51-34)40(53-41)36-30(50-38)10-8-27(48-36)14-23(43)15-28-32(17-31(47-26)22(20)3)49-33(35(28)45-4)16-24(44)19-42/h20,24-40,44H,2-3,5-19,42H2,1,4H3/t20-,24+,25+,26+,27-,28+,29+,30+,31-,32+,33-,34-,35-,36+,37+,38+,39-,40+,41+/m1/s1
| StdInChI = 1S/C40H59NO11/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41/h19,23-39,43H,2-3,5-18,41H2,1,4H3/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IGHZKAIPGTYWLF-FAXVPLPQSA-N
| StdInChIKey = UFNVPOGXISZXJD-JBQZKEIOSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}
'''Eribulin''' is an [[anticancer drug]] marketed by [[Eisai Co.]] under the trade name '''Halaven'''. Eribulin is also known as E7389 and ER-086526, and also carries the US NCI designation NSC-707389. It is used to treat certain patients with breast cancer and liposarcoma.


'''Eribulin''', sold under the brand name '''Halaven''' among others, is an [[anti-cancer medication]] used to treat [[breast cancer]] and [[liposarcoma]].<ref name="Halaven FDA label">{{cite web | title=Halaven- eribulin mesylate injection | website=DailyMed | date=22 December 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31ce4750-ded5-4a0b-95e9-f229fa6bc822 | access-date=9 July 2020}}</ref><ref name="Halaven EPAR" />
==Intellectual Property==


The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weakness or numbness in the hands and feet (peripheral neuropathy), abdominal pain and fever (pyrexia).<ref name="FDA-lipo2016" /> Eribulin may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium.<ref name="FDA-lipo2016" />
Currently there are 5 active patents in the United States that are associated with the '''Halaven''' drug application, N201532. The first one expires on June 16, 2019, the last one (USRE46965) expires on Jan 08, 2027.<ref>https://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=201532&Appl_type=N{{full citation needed|date=November 2017}}</ref>


Eribulin was approved for medical use in the United States in November 2010,<ref>{{cite web | title=Drug Approval Package: Halaven (erbulin mesylate) NDA 201532 | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201532s000_halaven_TOC.cfm | access-date=9 July 2020}}</ref> the European Union in March 2011,<ref name="Halaven EPAR" /> and Canada in December 2011.<ref name="CA Halaven PI">{{cite web | title=Halaven Product information | website=[[Health Canada]] | date=22 October 2009 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=86314 | access-date=16 December 2023}}</ref><ref>{{cite web | title=Halaven for Metastatic Breast Cancer | website=Canadian Agency for Drugs and Technologies in Health | date=9 March 2015 | url=https://www.cadth.ca/halaven-metastatic-breast-cancer-details | access-date=9 July 2020}}</ref><ref>{{cite press release | title=Eisai Announces Canadian Approval of its Anticancer Agent Halaven | website=Eisai Co., Ltd. | url=https://www.eisai.com/news/news201179.html | access-date=9 July 2020}}</ref> It is available as a [[generic medication]].<ref name="Mevlyq EPAR" />
==Approvals and indications==


== Medical uses ==
===Breast cancer===
The [[mesylate]] salt was approved by the [[U.S. Food and Drug Administration]] on November 15, 2010, to treat patients with [[metastatic breast cancer]] who have received at least two prior chemotherapy regimens for late-stage disease, including both [[anthracycline]]- and [[taxane]]-based [[chemotherapy|chemotherapies]].<ref>{{cite press release | title = FDA approves new treatment option for late-stage breast cancer | publisher = USFDA | date = 2010-11-15 | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm | accessdate = November 15, 2010}}</ref> It was approved by [[Health Canada]] on December 14, 2011, for treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease.<ref>[http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_halaven_141946-eng.php Notice of Decision for HALAVEN]{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Metastatic breast cancer impacts about 150,000 people in the USA, due to the patient population, Eisai was able to file and New Drug Application (NDA) under the orphan and rare disease designation.<ref>https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/drugandbiologicapprovalreports/ndaandblaapprovalreports/ucm544019.pdf{{full citation needed|date=November 2017}}</ref><ref>https://www.fda.gov/downloads/drugs/developmentapprovalprocess/smallbusinessassistance/ucm447307.pdf{{full citation needed|date=November 2017}}</ref>
Eribulin is [[indicated]] for the treatment of people with locally advanced or metastatic breast cancer,<ref name="Halaven EPAR" /><ref>{{cite press release | title = FDA approves new treatment option for late-stage breast cancer | publisher = U.S. [[Food and Drug Administration]] (FDA) | date = 15 November 2010 | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm | access-date = 15 November 2010 | archive-url = https://web.archive.org/web/20101117013510/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm | archive-date = 17 November 2010 | url-status = dead }}</ref><ref>{{cite web | title=Eribulin | website=U.S. Food and Drug Administration | date=28 January 2016 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/eribulin | access-date=16 December 2023}}</ref><ref>[http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_halaven_141946-eng.php Notice of Decision for Halaven]{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref>{{cite web | title=Halaven for Metastatic Breast Cancer | website=Canadian Agency for Drugs and Technologies in Health | date=9 March 2015 | url=https://www.cadth.ca/halaven-metastatic-breast-cancer-details | access-date=9 July 2020}}</ref><ref>{{cite press release | title=Eisai Announces Canadian Approval of its Anticancer Agent Halaven | website=Eisai Co., Ltd. | url=https://www.eisai.com/news/news201179.html | access-date=9 July 2020}}</ref> and for the treatment of adults with unresectable liposarcoma.<ref name="Halaven EPAR" /><ref name="FDA-lipo2016">{{cite press release | title=FDA approves first drug to show survival benefit in liposarcoma | website=U.S. [[Food and Drug Administration]] (FDA) | date=28 January 2016 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-show-survival-benefit-liposarcoma | access-date=9 July 2020}} {{PD-notice}}</ref><ref>{{cite press release | title=U.S. FDA Approves Eisai's Anticancer Agent Halaven For The Treatment Of Advanced Liposarcoma | publisher=Eisai Co., Ltd. | date=29 January 2016 | url=https://www.eisai.com/news/news201604.html | access-date=15 February 2021}}</ref>


== Adverse effects ==
===Liposarcoma===
Serious side effects may include anaemia; decrease in white blood cell count, which can increase the risk of serious infections that could lead to death; hair loss; cancer-related fatigue; numbness, tingling or burning in the hands and feet (neuropathy); harm to a developing fetus; as well as changes in heartbeat (QTc prolongation), that may also lead to death.<ref name="FDA-lipo2016" /><ref>{{cite web |date=5 June 2015 |title=Eribulin (Halaven) |url=https://breastcancernow.org/information-support/facing-breast-cancer/going-through-treatment-breast-cancer/chemotherapy/eribulin-halaven |access-date=15 September 2022 |website=Breast Cancer Now }}</ref>{{Unreliable medical source|date=December 2023}}
On January 28, 2016 the US FDA approved Halaven for the treatment of inoperable [[liposarcoma]] in patients who received prior chemotherapy that contained an [[anthracycline]] drug.<ref name=FDA-lipo2016>[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483714.htm FDA approves first drug to show survival benefit in liposarcoma. Jan 2016]</ref> A phase III trial reported: With Halaven the median [[overall survival]] for patients with liposarcoma was 15.6 months, compared to 8.4 months for patients treated with [[dacarbazine]].<ref name=FDA-lipo2016/>


==Structure and mechanism==
==Clinical trials==
Eribulin is a fully synthetic [[macrocyclic]] [[ketone]] [[analog (chemistry)|analog]] of the marine [[natural product]] [[halichondrin B]],<ref name="pmid11221827">{{cite journal | vauthors = Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA | title = In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B | journal = Cancer Research | volume = 61 | issue = 3 | pages = 1013–21 | date = February 2001 | pmid = 11221827 }}</ref><ref name="isbn0-8493-1863-7">{{cite book | veditors = Newman DJ, Kingston DG, Cragg GM | title = Anticancer agents from natural products | publisher = Taylor & Francis | location = Washington, DC | year = 2005 | chapter = Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B | vauthors = Yu MJ, Kishi Y, Littlefield BA | author-link2 = Yoshito Kishi | isbn = 978-0-8493-1863-4 }}{{page needed|date=November 2017}}</ref> the parent molecule being a naturally occurring, potent [[mitotic inhibitor]] with a unique [[mechanism of action]]. The parent molecule was originally found in the [[demosponge|sponge]] ''[[Halichondria]] okadai''.<ref name = "Hirata_1986">{{cite journal| vauthors = Hirata Y, Uemura D |date=1 January 1986|title=Halichondrins - antitumor polyether macrolides from a marine sponge|journal=Pure and Applied Chemistry|volume=58|issue=5|pages=701–710|doi=10.1351/pac198658050701|s2cid=38138047 |issn=1365-3075|doi-access = free | title-link = doi }}</ref><ref name="pmid1874739">{{cite journal | vauthors = Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E | title = Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data | journal = The Journal of Biological Chemistry | volume = 266 | issue = 24 | pages = 15882–9 | date = August 1991 | doi = 10.1016/S0021-9258(18)98491-7 | pmid = 1874739 | doi-access = free | title-link = doi }}</ref>
Eribulin is also being investigated by Eisai Co. for use in a variety of other solid tumors, including [[non-small cell lung cancer]], [[prostate cancer]] and [[sarcoma]].<ref>http://www.clinicaltrials.gov/ct2/results?term=eribulin+OR+E7389{{full citation needed|date=November 2017}}</ref>


Eribulin is a mechanistically unique [[microtubule#Chemical effects on microtubule dynamics|inhibitor of microtubule dynamics]],<ref name="pmid16020666">{{cite journal | vauthors = Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L | title = The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth | journal = Molecular Cancer Therapeutics | volume = 4 | issue = 7 | pages = 1086–95 | date = July 2005 | pmid = 16020666 | doi = 10.1158/1535-7163.MCT-04-0345 | s2cid = 38459382 | doi-access = free | title-link = doi }}</ref><ref name="pmid18645010">{{cite journal | vauthors = Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA | title = Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase | journal = Molecular Cancer Therapeutics | volume = 7 | issue = 7 | pages = 2003–11 | date = July 2008 | pmid = 18645010 | pmc = 2562299 | doi = 10.1158/1535-7163.MCT-08-0095 }}</ref> binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.<ref name="pmid20030375">{{cite journal | vauthors = Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA | title = Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability | journal = Biochemistry | volume = 49 | issue = 6 | pages = 1331–7 | date = February 2010 | pmid = 20030375 | pmc = 2846717 | doi = 10.1021/bi901810u }}</ref><ref>{{cite journal | vauthors = Wilson L, Lopus M, Miller HP, Azarenko O, Riffle S, Smith JA, Jordan MA | title = Effects of eribulin on microtubule binding and dynamic instability are strengthened in the absence of the βIII tubulin isotype | journal = Biochemistry | volume = 54 | issue = 42 | pages = 6482–9 | date = October 2015 | pmid = 26435331 | doi = 10.1021/acs.biochem.5b00745 }}</ref>
==Research and development==
Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein [[apoptosis]] of cancer cells is induced following prolonged and irreversible mitotic blockade.<ref name="pmid15313917">{{cite journal | vauthors = Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA | title = Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389 | journal = Cancer Research | volume = 64 | issue = 16 | pages = 5760–6 | date = August 2004 | pmid = 15313917 | doi = 10.1158/0008-5472.CAN-04-1169 | s2cid = 30919443 | doi-access = free | title-link = doi }}</ref><ref name="pmid21127197">{{cite journal | vauthors = Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ, Littlefield BA | title = Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions | journal = Cancer Research | volume = 71 | issue = 2 | pages = 496–505 | date = January 2011 | pmid = 21127197 | doi = 10.1158/0008-5472.CAN-10-1874 | doi-access = free | title-link = doi }}</ref> In addition to its cytotoxic, antimitotic-based mechanisms, preclinical studies in human breast cancer models have shown that eribulin also exerts complex effects on the biology of surviving cancer cells and residual tumors that appear unrelated to its antimitotic effects. These non-mitotic mechanisms include vascular remodeling that leads to increased tumor perfusion and mitigation of tumor [[Tumor hypoxia|hypoxia]], phenotypic changes consistent with reversal of [[epithelial-mesenchymal transition]] (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model.<ref name="pmid25060424">{{cite journal | vauthors = Funahashi Y, Okamoto K, Adachi Y, Semba T, Uesugi M, Ozawa Y, Tohyama O, Uehara T, Kimura T, Watanabe H, Asano M, Kawano S, Tizon X, McCracken PJ, Matsui J, Aoshima K, Nomoto K, Oda Y | title = Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models | journal = Cancer Science | volume = 105 | issue = 10 | pages = 1334–42 | date = October 2014 | pmid = 25060424 | pmc = 4462349 | doi = 10.1111/cas.12488 }}</ref><ref name="pmid24569463">{{cite journal | vauthors = Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, Matsui J | title = Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states | journal = British Journal of Cancer | volume = 110 | issue = 6 | pages = 1497–505 | date = March 2014 | pmid = 24569463 | pmc = 3960630 | doi = 10.1038/bjc.2014.80 }}</ref> In other studies, eribulin treatment of [[leiomyosarcoma]] and [[liposarcoma]] cells leads to increased expression of [[smooth muscle]] and [[adipocyte]] differentiation antigens, respectively.<ref name="pmid27069131">{{cite journal | vauthors = Kawano S, Asano M, Adachi Y, Matsui J | title = Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma | journal = Anticancer Research | volume = 36 | issue = 4 | pages = 1553–61 | date = April 2016 | pmid = 27069131 }}</ref> Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1).<ref name="pmid25378644">{{cite journal | vauthors = Laughney AM, Kim E, Sprachman MM, Miller MA, Kohler RH, Yang KS, Orth JD, Mitchison TJ, Weissleder R | title = Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin | journal = Science Translational Medicine | volume = 6 | issue = 261 | pages = 261ra152 | date = November 2014 | pmid = 25378644 | pmc = 4330962 | doi = 10.1126/scitranslmed.3009318 }}</ref> Fluorescently labeled eribulin has been used to study the [[pharmacokinetics]] and [[pharmacodynamics]] at single cell level ''in vivo''.<ref name="pmid25378644"/>
Two new eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is currently in Phase 1 clinical trials.<ref>https://clinicaltrials.gov/ct2/show/NCT03207672?cond=E7389+Liposomal&rank=1{{full citation needed|date=November 2017}}</ref> Preliminary in vivo experiments show a decrease in C(max) and a longer half-life with the liposomal formulation.<ref name=pmid23313921>{{cite journal |doi=10.1016/j.ijpharm.2013.01.010 |pmid=23313921 |title=Characterization of the pharmacokinetics of a liposomal formulation of eribulin mesylate (E7389) in mice |journal=International Journal of Pharmaceutics |volume=443 |issue=1–2 |pages=9–16 |year=2013 |last1=Yu |first1=Yanke |last2=Desjardins |first2=Christopher |last3=Saxton |first3=Phil |last4=Lai |first4=George |last5=Schuck |first5=Edgar |last6=Wong |first6=Y. Nancy }}</ref> The drug antibody eribulin combination therapy is a joint venture between Eisai and Merck. The clinical trials combine eribulin and [[pembrolizumab]], a [[PD-1 inhibitor]], for the treatment of breast cancer and other advanced cancers.<ref>https://clinicaltrials.gov/ct2/show/NCT03222856?term=eribulin+and+pembrolizumab&rank=1{{full citation needed|date=November 2017}}</ref>


The synthesis of eribulin was first published<ref>{{cite journal | vauthors = Seletsky BM, Wang Y, Hawkins LD, Palme MH, Habgood GJ, DiPietro LV, Towle MJ, Salvato KA, Wels BF, Aalfs KK, Kishi Y, Littlefield BA, Yu MJ | title = Structurally simplified macrolactone analogues of halichondrin B | journal = Bioorganic & Medicinal Chemistry Letters | volume = 14 | issue = 22 | pages = 5547–50 | date = November 2004 | pmid = 15482921 | doi = 10.1016/j.bmcl.2004.08.068 }}</ref> in 2001; a new synthetic route to the drug was published in 2009.<ref name="pmid19807076">{{cite journal | vauthors = Kim DS, Dong CG, Kim JT, Guo H, Huang J, Tiseni PS, Kishi Y | title = New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach | journal = Journal of the American Chemical Society | volume = 131 | issue = 43 | pages = 15636–41 | date = November 2009 | pmid = 19807076 | doi = 10.1021/ja9058475 }}</ref>
==Structure and mechanism==
Eribulin is a fully synthetic [[macrocyclic]] [[ketone]] [[analog (chemistry)|analogue]] of the marine [[natural product]] [[halichondrin B]],<ref name="pmid11221827">{{cite journal |pmid=11221827 |year=2001 |author1=Towle |first1=M. J |title=In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B |journal=Cancer Research |volume=61 |issue=3 |pages=1013–21 |last2=Salvato |first2=K. A |last3=Budrow |first3=J |last4=Wels |first4=B. F |last5=Kuznetsov |first5=G |last6=Aalfs |first6=K. K |last7=Welsh |first7=S |last8=Zheng |first8=W |last9=Seletsky |first9=B. M |last10=Palme |first10=M. H |last11=Habgood |first11=G. J |last12=Singer |first12=L. A |last13=Dipietro |first13=L. V |last14=Wang |first14=Y |last15=Chen |first15=J. J |last16=Quincy |first16=D. A |last17=Davis |first17=A |last18=Yoshimatsu |first18=K |last19=Kishi |first19=Y |last20=Yu |first20=M. J |last21=Littlefield |first21=B. A }}</ref><ref name="isbn0-8493-1863-7">{{cite book | editor = Newman DJ, Kingston DGI, Cragg, GM | authorlink = | others = | title = Anticancer agents from natural products | edition = | language = | publisher = Taylor & Francis | location = Washington, DC | year = 2005 | chapter = Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B | author = Yu MJ, [[Kishi Y]], Littlefield BA | quote = | isbn = 978-0-8493-1863-4 | oclc = | doi = | accessdate = }}{{page needed|date=November 2017}}</ref> the parent molecule being a potent naturally occurring [[mitotic inhibitor]] with a unique [[mechanism of action]] found in the [[demosponge|sponge]] genus ''[[Halichondria]]''.<ref name="Hirata_1986">{{cite journal |doi=10.1351/pac198658050701 |title=Halichondrins - antitumor polyether macrolides from a marine sponge |journal=Pure and Applied Chemistry |volume=58 |issue=5 |pages=701–710 |year=1986 |last1=Hirata |first1=Y |last2=Uemura |first2=D }}</ref><ref name="pmid1874739">{{cite journal |pmid=1874739 |year=1991 |author1=Bai |first1=R. L |title=Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data |journal=The Journal of Biological Chemistry |volume=266 |issue=24 |pages=15882–9 |last2=Paull |first2=K. D |last3=Herald |first3=C. L |last4=Malspeis |first4=L |last5=Pettit |first5=G. R |last6=Hamel |first6=E }}</ref>


==Research==
Eribulin is a mechanistically unique [[microtubule#Chemical effects on microtubule dynamics|inhibitor of microtubule dynamics]],<ref name="pmid16020666">{{cite journal |doi=10.1158/1535-7163.MCT-04-0345 |pmid=16020666 |title=The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth |journal=Molecular Cancer Therapeutics |volume=4 |issue=7 |pages=1086–95 |year=2005 |last1=Jordan |first1=M. A |last2=Kamath |first2=K |last3=Manna |first3=T |last4=Okouneva |first4=T |last5=Miller |first5=H. P |last6=Davis |first6=C |last7=Littlefield |first7=B. A |last8=Wilson |first8=L }}</ref><ref name="pmid18645010">{{cite journal |doi=10.1158/1535-7163.MCT-08-0095 |pmid=18645010 |pmc=2562299 |title=Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase |journal=Molecular Cancer Therapeutics |volume=7 |issue=7 |pages=2003–11 |year=2008 |last1=Okouneva |first1=T |last2=Azarenko |first2=O |last3=Wilson |first3=L |last4=Littlefield |first4=B. A |last5=Jordan |first5=M. A }}</ref> binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.<ref name="pmid20030375">{{cite journal |doi=10.1021/bi901810u |pmid=20030375 |pmc=2846717 |title=Eribulin Binds at Microtubule Ends to a Single Site on Tubulin to Suppress Dynamic Instability |journal=Biochemistry |volume=49 |issue=6 |pages=1331–7 |year=2010 |last1=Smith |first1=Jennifer A |last2=Wilson |first2=Leslie |last3=Azarenko |first3=Olga |last4=Zhu |first4=Xiaojie |last5=Lewis |first5=Bryan M |last6=Littlefield |first6=Bruce A |last7=Jordan |first7=Mary Ann }}</ref><ref>{{cite journal |doi=10.1021/acs.biochem.5b00745 |pmid=26435331 |title=Effects of Eribulin on Microtubule Binding and Dynamic Instability Are Strengthened in the Absence of the βIII Tubulin Isotype |journal=Biochemistry |volume=54 |issue=42 |pages=6482–9 |year=2015 |last1=Wilson |first1=Leslie |last2=Lopus |first2=Manu |last3=Miller |first3=Herbert P |last4=Azarenko |first4=Olga |last5=Riffle |first5=Stephen |last6=Smith |first6=Jennifer A |last7=Jordan |first7=Mary Ann }}</ref>
Eribulin is being investigated for use in a variety of solid tumors, including [[breast cancer]], [[non-small cell lung cancer]], [[prostate cancer]], [[Brain tumor|brain cancer]], [[cervical cancer]], [[Transitional cell carcinoma|urothelial cancer]], [[melanoma]], [[solitary fibrous tumor]]s, and various [[sarcoma]]s.<ref>{{cite web | title = 184 Studies found for: eribulin OR E7389 | url = http://www.clinicaltrials.gov/ct2/results?term=eribulin+OR+E7389 | work = ClinicalTrials.gov | publisher = U.S. National Library of Medicine}}</ref>
Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein [[apoptosis]] of cancer cells is induced following prolonged and irreversible mitotic blockade.<ref name="pmid15313917">{{cite journal |doi=10.1158/0008-5472.CAN-04-1169 |pmid=15313917 |title=Induction of Morphological and Biochemical Apoptosis following Prolonged Mitotic Blockage by Halichondrin B Macrocyclic Ketone Analog E7389 |journal=Cancer Research |volume=64 |issue=16 |pages=5760–6 |year=2004 |last1=Kuznetsov |first1=Galina |last2=Towle |first2=Murray J |last3=Cheng |first3=Hongsheng |last4=Kawamura |first4=Takanori |last5=Tendyke |first5=Karen |last6=Liu |first6=Diana |last7=Kishi |first7=Yoshito |last8=Yu |first8=Melvin J |last9=Littlefield |first9=Bruce A }}</ref><ref name="pmid21127197">{{cite journal |doi=10.1158/0008-5472.CAN-10-1874 |pmid=21127197 |title=Eribulin Induces Irreversible Mitotic Blockade: Implications of Cell-Based Pharmacodynamics for in vivo Efficacy under Intermittent Dosing Conditions |journal=Cancer Research |volume=71 |issue=2 |pages=496–505 |year=2010 |last1=Towle |first1=M. J |last2=Salvato |first2=K. A |last3=Wels |first3=B. F |last4=Aalfs |first4=K. K |last5=Zheng |first5=W |last6=Seletsky |first6=B. M |last7=Zhu |first7=X |last8=Lewis |first8=B. M |last9=Kishi |first9=Y |last10=Yu |first10=M. J |last11=Littlefield |first11=B. A }}</ref> In addition to its cytotoxic, antimitotic-based mechanisms, preclinical studies in human breast cancer models have shown that eribulin also exerts complex effects on the biology of surviving cancer cells and residual tumors that appear unrelated to its antimitotic effects. These non-mitotic mechanisms include vascular remodeling that leads to increased tumor perfusion and mitigation of tumor [[Tumor hypoxia|hypoxia]], phenotypic changes consistent with reversal of [[epithelial-mesenchymal transition]] (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model.<ref name="pmid25060424">{{cite journal |doi=10.1111/cas.12488 |pmid=25060424 |pmc=4462349 |title=Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models |journal=Cancer Science |volume=105 |issue=10 |pages=1334–42 |year=2014 |last1=Funahashi |first1=Yasuhiro |last2=Okamoto |first2=Kiyoshi |last3=Adachi |first3=Yusuke |last4=Semba |first4=Taro |last5=Uesugi |first5=Mai |last6=Ozawa |first6=Yoichi |last7=Tohyama |first7=Osamu |last8=Uehara |first8=Taisuke |last9=Kimura |first9=Takayuki |last10=Watanabe |first10=Hideki |last11=Asano |first11=Makoto |last12=Kawano |first12=Satoshi |last13=Tizon |first13=Xavier |last14=McCracken |first14=Paul J |last15=Matsui |first15=Junji |last16=Aoshima |first16=Ken |last17=Nomoto |first17=Kenichi |last18=Oda |first18=Yoshiya }}</ref><ref name="pmid24569463">{{cite journal |doi=10.1038/bjc.2014.80 |pmid=24569463 |pmc=3960630 |title=Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states |journal=British Journal of Cancer |volume=110 |issue=6 |pages=1497–505 |year=2014 |last1=Yoshida |first1=T |last2=Ozawa |first2=Y |last3=Kimura |first3=T |last4=Sato |first4=Y |last5=Kuznetsov |first5=G |last6=Xu |first6=S |last7=Uesugi |first7=M |last8=Agoulnik |first8=S |last9=Taylor |first9=N |last10=Funahashi |first10=Y |last11=Matsui |first11=J }}</ref> In other studies, eribulin treatment of [[leiomyosarcoma]] and [[liposarcoma]] cells leads to increased expression of [[smooth muscle]] and [[adipocyte]] differentiation antigens, respectively.<ref name="pmid27069131">{{cite journal |pmid=27069131 |year=2016 |author1=Kawano |first1=S |title=Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma |journal=Anticancer Research |volume=36 |issue=4 |pages=1553–61 |last2=Asano |first2=M |last3=Adachi |first3=Y |last4=Matsui |first4=J }}</ref> Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1).<ref name="pmid25378644">{{cite journal |doi=10.1126/scitranslmed.3009318 |pmid=25378644 |title= Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin |journal=Science Translational Medicine |volume=6 |issue=261 |pages= 261ra152 |year=2014 | vauthors = Laughney AM, Kim E, Sprachman MM, Miller MA, Kohler RH, Yang KS, Orth JD, Mitchison TJ, Weissleder R |pmc=4330962}}</ref> Fluorescently labeled eribulin has been used to study the [[pharmacokinetics]] and [[pharmacodynamics]] at single cell level ''in vivo''.<ref name="pmid25378644"/>


Two eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is in Phase I clinical trials.<ref>{{ClinicalTrialsGov|NCT03207672|Study of E7389 Liposomal Formulation in Subjects With Solid Tumor}}</ref> Preliminary ''in vivo'' experiments show a decrease in C(max) and a longer half-life with the liposomal formulation.<ref name=pmid23313921>{{cite journal | vauthors = Yu Y, Desjardins C, Saxton P, Lai G, Schuck E, Wong YN | title = Characterization of the pharmacokinetics of a liposomal formulation of eribulin mesylate (E7389) in mice | journal = International Journal of Pharmaceutics | volume = 443 | issue = 1–2 | pages = 9–16 | date = February 2013 | pmid = 23313921 | doi = 10.1016/j.ijpharm.2013.01.010 }}</ref> The drug antibody eribulin combination therapy is a joint venture between Eisai and Merck. The clinical trials combine eribulin and [[pembrolizumab]], a [[PD-1 inhibitor]], for the treatment of breast cancer and other advanced cancers.<ref>{{ClinicalTrialsGov|NCT03222856|Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes (KELLY)}}</ref>
A new synthetic route to the drug was published in 2009.<ref name="pmid19807076">{{cite journal |doi=10.1021/ja9058475 |pmid=19807076 |title=New Syntheses of E7389 C14−C35 and Halichondrin C14−C38 Building Blocks: Double-Inversion Approach |journal=Journal of the American Chemical Society |volume=131 |issue=43 |pages=15636–41 |year=2009 |last1=Kim |first1=Dae-Shik |last2=Dong |first2=Cheng-Guo |last3=Kim |first3=Joseph T |last4=Guo |first4=Haibing |last5=Huang |first5=Jian |last6=Tiseni |first6=Paolo S |last7=Kishi |first7=Yoshito }}</ref>


==References==
== References ==
{{reflist}}
{{reflist}}

== External links ==


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Latest revision as of 03:55, 10 July 2024

Eribulin
Clinical data
Trade namesHalaven, Mevlyq
Other namesE7389, ER-086526, NSC-707389, eribulin mesilate (JAN JP), eribulin mesylate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa611007
License data
Pregnancy
category
Routes of
administration		Intravenous
Drug classAntineoplastic agent
ATC code
Legal status
Legal status
Identifiers
  • 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy- 26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy- 7,9-ethano-12,15-methano-9H,15H-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4H)-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.230.372 Edit this at Wikidata
Chemical and physical data
FormulaC40H59NO11
Molar mass729.908 g·mol−1
3D model (JSmol)
  • CC1CC2CCC3C(=C)CC(O3)CCC45CC6C(O4)C7C(O6)C(O5)C8C(O7)CCC(O8)CC(=O)CC9C(CC(C1=C)O2)OC(C9OC)CC(CN)O
  • InChI=1S/C40H59NO11/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41/h19,23-39,43H,2-3,5-18,41H2,1,4H3/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+/m1/s1 checkY
  • Key:UFNVPOGXISZXJD-JBQZKEIOSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Eribulin, sold under the brand name Halaven among others, is an anti-cancer medication used to treat breast cancer and liposarcoma.[4][5]

The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weakness or numbness in the hands and feet (peripheral neuropathy), abdominal pain and fever (pyrexia).[10] Eribulin may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium.[10]

Eribulin was approved for medical use in the United States in November 2010,[11] the European Union in March 2011,[5] and Canada in December 2011.[2][12][13] It is available as a generic medication.[6]

Medical uses

[edit]

Eribulin is indicated for the treatment of people with locally advanced or metastatic breast cancer,[5][14][15][16][17][18] and for the treatment of adults with unresectable liposarcoma.[5][10][19]

Adverse effects

[edit]

Serious side effects may include anaemia; decrease in white blood cell count, which can increase the risk of serious infections that could lead to death; hair loss; cancer-related fatigue; numbness, tingling or burning in the hands and feet (neuropathy); harm to a developing fetus; as well as changes in heartbeat (QTc prolongation), that may also lead to death.[10][20][unreliable medical source?]

Structure and mechanism

[edit]

Eribulin is a fully synthetic macrocyclic ketone analog of the marine natural product halichondrin B,[21][22] the parent molecule being a naturally occurring, potent mitotic inhibitor with a unique mechanism of action. The parent molecule was originally found in the sponge Halichondria okadai.[23][24]

Eribulin is a mechanistically unique inhibitor of microtubule dynamics,[25][26] binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.[27][28] Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein apoptosis of cancer cells is induced following prolonged and irreversible mitotic blockade.[29][30] In addition to its cytotoxic, antimitotic-based mechanisms, preclinical studies in human breast cancer models have shown that eribulin also exerts complex effects on the biology of surviving cancer cells and residual tumors that appear unrelated to its antimitotic effects. These non-mitotic mechanisms include vascular remodeling that leads to increased tumor perfusion and mitigation of tumor hypoxia, phenotypic changes consistent with reversal of epithelial-mesenchymal transition (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model.[31][32] In other studies, eribulin treatment of leiomyosarcoma and liposarcoma cells leads to increased expression of smooth muscle and adipocyte differentiation antigens, respectively.[33] Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1).[34] Fluorescently labeled eribulin has been used to study the pharmacokinetics and pharmacodynamics at single cell level in vivo.[34]

The synthesis of eribulin was first published[35] in 2001; a new synthetic route to the drug was published in 2009.[36]

Research

[edit]

Eribulin is being investigated for use in a variety of solid tumors, including breast cancer, non-small cell lung cancer, prostate cancer, brain cancer, cervical cancer, urothelial cancer, melanoma, solitary fibrous tumors, and various sarcomas.[37]

Two eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is in Phase I clinical trials.[38] Preliminary in vivo experiments show a decrease in C(max) and a longer half-life with the liposomal formulation.[39] The drug antibody eribulin combination therapy is a joint venture between Eisai and Merck. The clinical trials combine eribulin and pembrolizumab, a PD-1 inhibitor, for the treatment of breast cancer and other advanced cancers.[40]

References

[edit]
  1. ^ "Eribulin (Halaven) Use During Pregnancy". Drugs.com. 22 October 2019. Retrieved 9 July 2020.
  2. ^ a b "Halaven Product information". Health Canada. 22 October 2009. Retrieved 16 December 2023.
  3. ^ "Halaven 0.44 mg/ml solution for injection". (emc). 16 January 2023. Retrieved 16 December 2023.
  4. ^ a b "Halaven- eribulin mesylate injection". DailyMed. 22 December 2017. Retrieved 9 July 2020.
  5. ^ a b c d e "Halaven EPAR". European Medicines Agency (EMA). 17 March 2011. Retrieved 16 December 2023.
  6. ^ a b "Mevlyq EPAR". European Medicines Agency (EMA). 9 February 2024. Retrieved 19 February 2024.
  7. ^ "Mevlyq product information". Union Register of medicinal products. 13 February 2024. Retrieved 19 February 2024.
  8. ^ "Eisai Announces Japan Launch Of Anticancer Agent Halaven" (Press release). Eisai Co., Ltd. 19 July 2011. Retrieved 15 February 2021.
  9. ^ "Anticancer Agent Halaven Approved For Treatment Of Locally Advanced Or Metastatic Breast Cancer In China" (Press release). Eisai Co., Ltd. 17 July 2019. Retrieved 15 February 2021.
  10. ^ a b c d "FDA approves first drug to show survival benefit in liposarcoma". U.S. Food and Drug Administration (FDA) (Press release). 28 January 2016. Retrieved 9 July 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ "Drug Approval Package: Halaven (erbulin mesylate) NDA 201532". U.S. Food and Drug Administration (FDA). Retrieved 9 July 2020.
  12. ^ "Halaven for Metastatic Breast Cancer". Canadian Agency for Drugs and Technologies in Health. 9 March 2015. Retrieved 9 July 2020.
  13. ^ "Eisai Announces Canadian Approval of its Anticancer Agent Halaven". Eisai Co., Ltd. (Press release). Retrieved 9 July 2020.
  14. ^ "FDA approves new treatment option for late-stage breast cancer" (Press release). U.S. Food and Drug Administration (FDA). 15 November 2010. Archived from the original on 17 November 2010. Retrieved 15 November 2010.
  15. ^ "Eribulin". U.S. Food and Drug Administration. 28 January 2016. Retrieved 16 December 2023.
  16. ^ Notice of Decision for Halaven[permanent dead link‍]
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  37. ^ "184 Studies found for: eribulin OR E7389". ClinicalTrials.gov. U.S. National Library of Medicine.
  38. ^ Clinical trial number NCT03207672 for "Study of E7389 Liposomal Formulation in Subjects With Solid Tumor" at ClinicalTrials.gov
  39. ^ Yu Y, Desjardins C, Saxton P, Lai G, Schuck E, Wong YN (February 2013). "Characterization of the pharmacokinetics of a liposomal formulation of eribulin mesylate (E7389) in mice". International Journal of Pharmaceutics. 443 (1–2): 9–16. doi:10.1016/j.ijpharm.2013.01.010. PMID 23313921.
  40. ^ Clinical trial number NCT03222856 for "Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes (KELLY)" at ClinicalTrials.gov
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